chr17-80037932-G-T

Variant names:

• chr17-80037932-G-T
• rs3764439
• NM_017950.4:c.30-191G>T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_017950.4(CCDC40):​c.30-191G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.13 in 548,826 control chromosomes in the GnomAD database, including 5,049 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.13 (1274 hom., cov: 31)
  • Exomes 𝑓: 0.13 (3775 hom.)
• Consequence: CCDC40 NM_017950.4 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.213
• Publications: 4 publications found

Genes affected

CCDC40 (HGNC:26090): (coiled-coil domain 40 molecular ruler complex subunit) This gene encodes a protein that is necessary for motile cilia function. It functions in correct left-right axis formation by regulating the assembly of the inner dynein arm and the dynein regulatory complexes, which control ciliary beat. Mutations in this gene cause ciliary dyskinesia type 15, a disorder due to defects in cilia motility. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2011]

CCDC40 Gene-Disease associations (from GenCC):

• primary ciliary dyskinesia 15

  Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: G2P, ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), PanelApp Australia, Laboratory for Molecular Medicine
• primary ciliary dyskinesia

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• autoimmune disease

  Inheritance: AR Classification: LIMITED Submitted by: Ambry Genetics

ACMG classification

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.88).
• BP6: Variant 17-80037932-G-T is Benign according to our data. Variant chr17-80037932-G-T is described in ClinVar as [Benign]. Clinvar id is 1269480.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.155 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CCDC40	NM_017950.4	c.30-191G>T		intron_variant	Intron 1 of 19	ENST00000397545.9	NP_060420.2
CCDC40	NM_001243342.2	c.30-191G>T		intron_variant	Intron 1 of 17		NP_001230271.1
CCDC40	NM_001330508.2	c.30-191G>T		intron_variant	Intron 1 of 10		NP_001317437.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CCDC40	ENST00000397545.9	c.30-191G>T		intron_variant	Intron 1 of 19	5	NM_017950.4	ENSP00000380679.4

Frequencies

GnomAD3 genomes AF: 0.126 AC: 19047 AN: 151632 Hom.: 1276 Cov.: 31

Gnomad AFR AF: 0.120

Gnomad AMI AF: 0.0275

Gnomad AMR AF: 0.0771

Gnomad ASJ AF: 0.124

Gnomad EAS AF: 0.165

Gnomad SAS AF: 0.115

Gnomad FIN AF: 0.162

Gnomad MID AF: 0.171

Gnomad NFE AF: 0.133

Gnomad OTH AF: 0.127

GnomAD4 exome AF: 0.132 AC: 52513 AN: 397074 Hom.: 3775 Cov.: 3 AF XY: 0.133 AC XY: 28439 AN XY: 213670

African (AFR) AF: 0.121 AC: 1252 AN: 10380

American (AMR) AF: 0.0717 AC: 1332 AN: 18566

Ashkenazi Jewish (ASJ) AF: 0.121 AC: 1516 AN: 12484

East Asian (EAS) AF: 0.182 AC: 4427 AN: 24290

South Asian (SAS) AF: 0.129 AC: 6308 AN: 48754

European-Finnish (FIN) AF: 0.167 AC: 5332 AN: 31894

Middle Eastern (MID) AF: 0.167 AC: 273 AN: 1634

European-Non Finnish (NFE) AF: 0.129 AC: 29369 AN: 227684

Other (OTH) AF: 0.126 AC: 2704 AN: 21388

GnomAD4 genome AF: 0.126 AC: 19045 AN: 151752 Hom.: 1274 Cov.: 31 AF XY: 0.127 AC XY: 9380 AN XY: 74140

African (AFR) AF: 0.120 AC: 4964 AN: 41346

American (AMR) AF: 0.0770 AC: 1172 AN: 15226

Ashkenazi Jewish (ASJ) AF: 0.124 AC: 430 AN: 3466

East Asian (EAS) AF: 0.164 AC: 845 AN: 5144

South Asian (SAS) AF: 0.115 AC: 554 AN: 4808

European-Finnish (FIN) AF: 0.162 AC: 1702 AN: 10510

Middle Eastern (MID) AF: 0.163 AC: 48 AN: 294

European-Non Finnish (NFE) AF: 0.133 AC: 9037 AN: 67938

Other (OTH) AF: 0.127 AC: 268 AN: 2110

Alfa AF: 0.135 Hom.: 328

Bravo AF: 0.117

Asia WGS AF: 0.128 AC: 446 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Jul 09, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.88
CADD	Benign	5.0
DANN	Benign	0.53
PhyloP100		-0.21
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs3764439; hg19: chr17-78011731;